Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities, Crohn's disease and ulcerative colitis. Accumulated evidence indicates that an aberrant immune activation caused by the interplay of genetic susceptibility and environmental impact on the gut microbiota may be involved in the pathogenesis of IBD. Rapid advances in next-generation sequencing technology have enabled a number of studies to identify the alteration of the gut microbiota, termed dysbiosis, in IBD. Moreover, the alteration in the metabolites derived from the gut microbiota in IBD has also been described in many studies. Therefore, microbiota-based interventions such as fecal microbiota transplantation (FMT) have attracted attention as a novel therapeutic option in IBD. However, in clinical trials, the efficacy of FMT for IBD remains controversial. Additional basic and clinical studies are required to validate whether FMT can assume a complementary role in the treatment of IBD. The present review provides a synopsis on dysbiosis in IBD and on the association between the gut microbiota and the pathogenesis of IBD. In addition, we summarize the use of probiotics in IBD and the results of current clinical trials of FMT for IBD.

Keywords: Dysbiosis; Fecal microbiota transplantation; Inflammatory bowel disease; Probiotics; Short chain fatty acid.

Figure 1

Function of butyrate in intestinal mucosa. Butyrate contributes to the maintenance of gut homeostasis by multiple mechanisms. Butyrate is mainly produced in the intestinal tract by bacteria of the Firmicutes phylum during fermentation of dietary fibers under anaerobic conditions. Butyrate is the main energy source for the intestinal epithelial cells. (1) The genus Clostridium promotes the differentiation and proliferation of regulatory T cells by enhancing the production of transforming growth factor β from intestinal epithelial cells; (2) Butyrate enhances the production of the anti-inflammatory cytokine, interleukin-10, produced by macrophages and dendritic cells through GPR109a, which is the G protein-coupled receptor for butyrate; and (3) Butyrate upregulates histone H3 acetylation at regulatory regions of the Foxp3 gene and promotes the differentiation of naïve CD4⁺ T cells into regulatory T cells. IL: Interleukin.